Project Description The base of the tongue (posterior to the terminal sulcus) is anatomically, physiologically, and functionally distinct from its body (from the sulcus to the tip). Whereas the tongue body subserves drinking, ingestion, mastication, and articulation, the tongue base is part of the pharynx and controls the entrances of the larynx and esophagus during respiration, swallowing, and vocalization. The tongue base is the primary locus for adipose tissue accumulation in the oropharyngeal region, and its resultant volumetric increase is likely a major player in obstructive sleep apnea (OSA), a serious breathing disorder affecting 20% of the population with significant morbidity and mortality. The tongue base is also subject to conditions that decrease its volume, such as surgical volumetric reduction (partial glossectomy) to ameliorate OSA, and more commonly to treat oral cancer patients. Since the tongue base is where all extrinsic tongue muscles insert, adipose tissue accumulation may not only increase its volume, but interfere with muscle contraction, affecting its ability to stabilize the oropharyngeal airway and changing its kinematics in respiration and swallowing. It is unknown how the tongue base and other oropharyngeal structures respond to these volumetric changes and to what extent the tongue tissues are capable of regeneration after surgical injury or infiltration of adipose tissue. Indeed, our understanding of the tongue base is very rudimentary compared to knowledge of the tongue body and other skeletal muscles. The present application builds on our previous work in studying the tongue body in a large-animal model, the miniature pig. Herein we propose to investigate the functional (respiration and swallowing) and morphological (spatial configuration of oropharynx) consequences of the volumetric alteration of the tongue base and to elucidate its reparative capacity through a study of its stem cell population - satellite cells. The overall hypothesis is that volumetric increase of the tongue base aids swallowing at the expense of oropharyngeal airway patency whereas volumetric decrease has the opposite effects. Further, we will establish the potential for myogenic repair of the tongue base by assessing its satellite cells in comparison to other skeletal muscles, and link these regenerative potentials to functional outcomes. The 1st Aim is to ascertain how tongue base behavior subserves respiration and swallowing; the 2nd Aim is to evaluate how tongue base volumetric changes affect respiration, swallowing, and the oropharyngeal space; and the 3rd Aim is to assess healing after volumetric changes of the tongue base and to establish whether satellite cells in the tongue base enable myogenesis to repair muscle function. The overall hypothesis is that volumetric increase of the tongue base aids swallowing at the expense of oropharyngeal airway patency whereas volumetric decrease has the opposite effects. The outcomes will lead to new understanding of how the tongue base participates in oropharyngeal function and dysfunction, and provide new knowledge about its muscle biology, wound healing, and functional recovery, which will help clinicians to develop better treatment strategies for oral cancers, OSA, and other oropharyngeal disorders.